Despite its size and rigidity, the cell nucleus can be moved or reorganized by cytoskeletal filaments under various conditions (for example, during viral infection) 1 – 11 . Moreover, whereas chromatin organizes into non-random domains 12 , extensive heterogeneity at the single-cell level 13 means that precisely how and why nuclei reorganize remains an area of intense investigation. Here we describe convolutional neural network-based automated cell classification and analysis pipelines, which revealed the extent to which human cytomegalovirus generates nuclear polarity through a virus-assembled microtubule-organizing centre. Acetylation of tubulin enables microtubules emanating from this centre to rotate the nucleus by engaging cytoplasmically exposed dynein-binding domains in the outer nuclear membrane protein nesprin-2G, which polarizes the inner nuclear membrane protein SUN1. This in turn creates intranuclear polarity in emerin, and thereby controls nuclear actin filaments that spatially segregate viral DNA from inactive histones and host DNA, maximizing virus replication. Our findings demonstrate the extent to which viruses can control the nucleus from the cytoplasm. Human cytomegalovirus rotates the nuclei of infected cells to set up intranuclear polarization and thereby separate viral DNA from inactive histones and associated host DNA.

中文翻译：

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人巨细胞病毒对核内极性的细胞质控制

尽管它的大小和刚性，细胞核可以在各种条件下（例如，在病毒感染期间） 1 – 11 的细胞骨架细丝移动或重组。此外，虽然染色质组织成非随机域 12，但单细胞水平 13 的广泛异质性意味着，确切地说，细胞核重组的方式和原因仍然是一个深入研究的领域。在这里，我们描述了基于卷积神经网络的自动细胞分类和分析管道，它揭示了人类巨细胞病毒通过病毒组装的微管组织中心产生核极性的程度。微管蛋白的乙酰化使从该中心发出的微管通过与外核膜蛋白 nesprin-2G 中细胞质暴露的动力蛋白结合域结合来旋转细胞核，使内核膜蛋白 SUN1 极化。这反过来在 emerin 中产生核内极性，从而控制核肌动蛋白丝，在空间上将病毒 DNA 与非活性组蛋白和宿主 DNA 隔离，最大限度地提高病毒复制。我们的研究结果证明了病毒可以从细胞质控制细胞核的程度。人类巨细胞病毒旋转受感染细胞的细胞核以建立核内极化，从而将病毒 DNA 与无活性的组蛋白和相关的宿主 DNA 分离。